RECRUITMENT AND ACTIVATION OF BROWN ADIPOCYTES AS PREVENTIVE AND CURATIVE THERAPY FOR TYPE 2 DIABETES

Triggered by the excessive expansion and dysfunction of adipose tissue in the obese state, type 2 diabetes and its associated complications have emerged as the leading causes of death in Western countries, associated with estimated health care costs of more than 30 billion Euros in the European Union per year. So far, effective, simple and non-surgical treatment strategies for “diabesity” are lacking. Consequently, in 2007 the European Commission published the white paper on “A Strategy for Europe on Nutrition, Overweight and Obesity related health issues” (COM 2007 279).

At the functional level, adipocytes can be subdivided into two distinct categories i.e. white and brown: Whereas white adipocytes are specialized in the storage of chemical energy in white adipose tissue (WAT) stores, brown adipocytes -located in BAT or WAT, the latter thus called “BRITE” (brown-in-white) - dissipate energy in the form of heat. If white adipocyte storage capacity is exceeded, this generates systemic lipotoxicity, leading to insulin resistance and eventually pancreatic beta-cell failure in the diabesity state. Intriguingly, functional and active BAT is inversely correlated with age and body mass index (BMI) in humans. Indeed, thermogenic BAT is a major site for lipid breakdown and glucose uptake, and thus the thermogenic capacity of even small amounts of brown adipocytes has emerged as an attractive target for anti-diabesity therapies.